The broad objective of this proposal is to apply modern computational and graphics methods to accelerate progress in solving biological problems. The focus here is in two main research areas. The first area involves development and use of computer methods for predicting RNA structure from sequence. Dr. Turner's group is developing computer methods for this purpose. New data are being obtained, particularly through the use of thermodynamics, two-dimensional NMR and chemical susceptibility studies, which will allow further refinements of these computer codes. Interpretation of these data will require modelling the complicated structures involved using molecular dynamics/mechanics calculations coupled with 3-dimensional stereo graphics display capabilities. These methods are also being applied by Dr. Lindahl to investigate regulation of the synthesis of ribosomal proteins and by Dr. Gorovsky to probe sequence - structure - function relationships in tetrahymena RNA. A second area of research will use molecular graphics and computational techniques to aid in the design and interpretation of a wide range of biochemical and biophysical experiments. The researchers involved (Drs. Krugh, McLendon, Turner, Kreilick and Kool) will study structural and mechanistic aspects of (among others) drug binding to oligonucleotides, electron transfer in proteins, self-splicing RNA, metalloenzyme structures, and DNA triple helix formation. Molecular dynamics simulations and accurate 3-dimensional visualization of the molecules involved will be critical for the design and analysis of the experiments. 500 MHz two-dimensional NMR experiments will be central to much of this proposed research. Intra- molecular distance estimates from NOESY data will be used to constrain energy minimization programs to determine the three-dimensional structure of biomolecules in solution.